The effect of new medical treatment for hereditary retinal degeneration based on its molecular pathogenesis

本研究项目的目的是调查遗传性视网膜变性即视网膜色素变性的相关基因，并根据分子遗传学分析所获得的分子发病机制的发现，研究治疗这些疾病的新药物的可能性。e.视网膜色素变性和相关疾病的分子遗传学分析，我们首先报道了GCAP 2基因是视网膜色素变性的一个致病基因，这是基于我们在三个独立的日本家族的患病成员中鉴定出GCAP 2基因中的相同突变的发现（Sato，Nakazawa，et al.，2005年）。我们将该基因作为视网膜色素变性的候选基因研究了5年多。进一步的基因型和表型研究表明，这种特殊的突变不仅与典型的视网膜色素变性有关，而且与视网膜色素变性伴黄斑变性有关。 ...更多信息 这表明GCAP 2基因突变可能与遗传异质性有关。此外，由于GCAP 2蛋白是一种钙结合蛋白，因此也提示钙离子在视网膜变性发生时可能发挥一定作用，这与GCAP 2基因突变有关。e.视网膜色素变性的新药物治疗，我们已经报道了钙拮抗剂对RCS大鼠和rd（视网膜变性）小鼠视网膜变性的实验治疗效果（Takano，Nakazawa，et al.，2004年）。这些实验动物研究有利地提示某些钙拮抗剂可能作为视网膜色素变性的光感受器保护剂发挥作用。我们进一步研究了antocyanine对实验性视网膜变性的影响。结果表明，它能延缓RCS大鼠视网膜变性的发生。这些结果表明，进一步的可用性antocyanine作为治疗剂视网膜色素变性。少

The aims of this research project are to investigate responsible genes for hereditary retinal degeneration namely retinitis pigmentosa and to examine the possibility for novel medical treatments for these diseases based on the findings of molecular pathogenesis that would be obtained by the molecular genetic analyzes.As for the first point, i. e. molecular genetic analysis for retinitis pigmentosa and allied diseases, we have first reported that the GCAP2 gene is one of the responsible genes for retinitis pigmentosa based on the findings that we had identified the same mutation in the GCAP2 gene in the affected members of three independent Japanese families (Sato, Nakazawa, et al.,2005). We had focused on this gene as a candidate gene for retinitis pigmentosa for more than 5 years. Moreover, the further genotype-and-phenotype study revealed that this particular mutation was associated with not only typical retinitis pigmentosa, but also retinitis pigmentosa associated with macular dege … More neration or solely macular degeneration, suggesting that the mutation in the GCAP2 gene may be related to genetic heterogeneity. In addition, because GCAP2 protein is a kind of calcium-binding protein, it is also suggested that calcium ion may play a certain role when retinal degeneration occurs in relation to the mutation in the GCAP2 gene.As for the second point, i. e. novel medical treatment for retinitis pigmentosa, we have already reported the experimental therapeutic effects of calcium antagonist on retinal degeneration of RCS rats and rd (retinal degeneration) mouse (Takano, Nakazawa, et al.,2004). These experimental animal studies favorably suggest the possibility that some of calcium antagonists may play as a photoreceptor-protective agents for retinitis pigmentosa. We further examined the effect of antocyanine on experimental retinal degeneration. Results indicate that it delays retinal degeneration of RCS rats electrophsyolosically. These results suggest further availability of antocyanine as a thrapeutic agent for retinitis pigmentosa. Less